tbuckley/cabot-search huggingface dataset:
Nina Cabezas Wallscheid: Enjoying the freedom to decide my research path
Authors: Lucie Van Emmenis
Journal: The Journal of Experimental Medicine (2023)

Nina Cabezas Wallscheid is a group leader at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany. Taking a multidisciplinary approach, her lab investigates the mechanisms by which metabolites regulate the epigenetic and metabolic state of hematopoietic stem cell fate in young and upon aging, with the aim to identify therapeutic strategies for nutritional and hematological diseases. We spoke to Nina recently to learn more about her long-term interest in cell regulation, the joys of being a group leader, and the adventures she goes on while outside of the lab.
Helen Salisbury: Playing to our strengths
Authors: Helen Salisbury
Journal: BMJ (2023)

Way back in the last century when I was a newly qualified doctor, I spent a lot of my time doing what we called scut work.This was the boring, repetitive, relatively unskilled work required to keep the ward running, tasks such as filling in forms and tracking down x rays.It made some sort of sense as we were definitely the lowest paid staff in the hospital, especially at weekends.It also contributed to the very long
“Ashamed and alone”—healthcare staff need better support after a patient’s suicide
Authors: Rachel Gibbons
Journal: BMJ (2023)

patient's suicide can have a detrimental impact on the wellbeing of healthcare staff and future patient care, says Rachel Gibbons Rachel Gibbons consultant psychiatrist and chair of the Working Group on the Effect of Suicide and Homicide Every surgeon carries within himself a small cemetery, where from time to time he goes to pray
Disulfide bridge-targeted metabolome mining unravels an antiparkinsonian peptide
Authors: Zhiwu Tong, Xiahong Xie, Huiming Ge, Ruihua Jiao, Tingting Wang, Xincun Wang, Wenying Zhuang, Gang Hu, Renxiang Tan
Journal: Acta Pharmaceutica Sinica B (2023)

Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics, thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical potentials. However, the success rate is decreasing, presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely 'overlooked' during the characterization effort. Here, we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP (ribosomally synthesized and post-translationally modified peptide), named acalitide, by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug molecules. Acalitide is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease (AcaB)-catalyzed lactamization of AcaA, an unprecedented precursor peptide. Such a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation strategy. Taken together, the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson's disease that is globally prevailing in an alarming manner.
Cover Image, Volume 43, Issue 9
Authors: Yaoping Shi, Donghua Shi, Jiachang Chi, Dan Cui, Xiaoyin Tang, Yan Lin, Siying Wang, Zonghai Li, Haojie Jin, Bo Zhai
Journal: Cancer Communications (2023)

The cover image is based on the Correspondence Combined local therapy and CAR-GPC3 T-cell therapy in advanced hepatocellular carcinoma: a proof-of-concept treatment strategy by Yaoping Shi et al., https://doi.org/10.1002/cac2.12472.
A foundational approach to culture and analyze malnourished organoids
Authors: Meryl Perlman, Stefania Senger, Smriti Verma, James Carey, Christina S. Faherty
Journal: Gut Microbes (2023)

The gastrointestinal (GI) epithelium plays a major role in nutrient absorption, barrier formation, and innate immunity. The development of organoid-based methodology has significantly impacted the study of the GI epithelium, particularly in the fields of mucosal biology, immunity, and host-microbe interactions. Various effects on the GI epithelium, such as genetics and nutrition, impact patients and alter disease states. Thus, incorporating these effects into organoid-based models will facilitate a better understanding of disease progression and offer opportunities to evaluate therapeutic candidates. One condition that has a significant effect on the GI epithelium is malnutrition, and studying the mechanistic impacts of malnutrition would enhance our understanding of several pathologies. Therefore, the goal of this study was to begin to develop methodology to generate viable malnourished organoids with accessible techniques and resources that can be used for a wide array of mechanistic studies. By selectively limiting distinct macronutrient components of organoid media, we were able to successfully culture and evaluate malnourished organoids. Genetic and protein-based analyses were used to validate the approach and confirm the presence of known biomarkers of malnutrition. Additionally, as proof-of-concept, we utilized malnourished organoid-derived monolayers to evaluate the effect of malnourishment on barrier formation and the ability of the bacterial pathogen Shigella flexneri to infect the GI epithelium. This work serves as the basis for new and exciting techniques to alter the nutritional state of organoids and investigate the related impacts on the GI epithelium.
Escalation Versus Induction/High-Efficacy Treatment Strategies for Relapsing Multiple Sclerosis: Which is Best for Patients?
Authors: Gilles Edan, Emmanuelle Le Page
Journal: Drugs (2023)

After more than 2 decades of recommending an escalating strategy for the treatment of most patients with multiple sclerosis, there has recently been considerable interest in the use of high-efficacy therapies in the early stage of the disease. Early intervention with induction/high-efficacy disease-modifying therapy may have the best risk-benefit profile for patients with relapsing-remitting multiple sclerosis who are young and have active disease, numerous focal T2 lesions on spinal and brain magnetic resonance imaging, and no irreversible disability. Although we have no curative treatment, at least seven classes of high-efficacy drugs are available, with two main strategies. The first strategy involves the use of high-efficacy drugs (e.g., natalizumab, sphingosine 1-phosphate receptor modulators, or anti-CD20 drugs) to achieve sustained immunosuppression. These can be used as a first-line therapy in many countries. The second strategy entails the use of one of the induction drugs (short-term use of mitoxantrone, alemtuzumab, cladribine, or autologous hematopoietic stem cell transplant) that are mainly recommended as a second-line or third-line treatment in patients with very active or aggressive multiple sclerosis disease. Early sustained immunosuppression exposes patients to heightened risks of infection and cancer proportionate to cumulative exposure, and induction drugs expose patients to similar risks during the initial post-treatment period, although these risks decrease over time. Their initial potential safety risks should now be revisited, taking account of long-term data and some major changes in their regimens: natalizumab with the long-term monitoring of John Cunningham virus; use of monthly courses of mitoxantrone with maximum cumulative doses of 36–72 mg/m2, followed by a safer disease-modifying drug; cladribine with only 2-weekly treatment courses required in years 1 and 2 and no systematic treatment for the following 2 years; alemtuzumab, whose safety and clinical impacts have now been documented for more than 6 years after the last infusion; and autologous haematopoietic stem cell transplant, which dramatically reduces transplantation-related mortality with a new regimen and guidelines. Escalation and induction/high-efficacy treatments need rigorous magnetic resonance imaging monitoring. Monitoring over the first few years, using the MAGNIMS score or American Academy of Neurology guidelines, considerably improves prediction accuracy and facilitates the selection of patients with relapsing-remitting multiple sclerosis requiring aggressive treatment.
Identification of combinatorial miRNA panels derived from extracellular vesicles as biomarkers for esophageal squamous cell carcinoma
Authors: Yaojie Wang, Xiaoya Li, Xiaojian Wei, Lei Li, Hanyu Bai, Xi Yan, Hongtao Zhang, Libo Zhao, Wei Zhou, Lianmei Zhao
Journal: MedComm (2023)

MicroRNAs (miRNAs) are relatively stable in blood, emerging as one of the most promising biomarkers in tumor liquid biopsy. Both total and extracellular vesicles (EVs) encapsulated miRNA have been studied for prognostic potential in a variety of cancers. Here, we systematically compared and verified the total and vesicle-derived miRNA expression profiles from plasma samples in healthy controls and patients with esophageal squamous cell carcinoma (ESCC). In the present study, four miRNA species miR-636, miR-7641, miR-28-3p, and miR-1246 that were differentially expressed in ESCC patients were chosen for further study. We first elucidated their essential function in ESCC progression and further explored their preliminary mechanism by identifying target proteins and involving signal pathways. Subsequently, the prognostic miRNA panels including miR-636, miR-7641, miR-1246, and miR-28-3p for ESCC diagnosis were constructed and validated using different cohort. Our results showed that the panel including the above four miRNAs derived from plasma EVs was most effective in distinguishing tumor patients from normal subjects, while integrated plasma EVs-derived miR-1246, miR-28-3p and total plasma miRNAs miR-636, miR-7641 showed the best capability in predicting lymph node metastasis. In summary, our studies revealed that plasma EVs-derived miRNAs could be emerged as promising biomarkers for ESCC diagnosis.
Integrative analysis of TROAP with molecular features, carcinogenesis, and related immune and pharmacogenomic characteristics in soft tissue sarcoma
Authors: Chao Tu, Binfeng Liu, Chenbei Li, Chengyao Feng, Hua Wang, Haixia Zhang, Shasha He, Zhihong Li
Journal: MedComm (2023)

Soft tissue sarcoma (STS) is an uncommon malignancy that often carries a grim prognosis. Trophinin-associated protein (TROAP) is augmented in a variety of tumors and can affect tumor proliferation. Nevertheless, the prognostic value and specific functions of TROAP in STS are still vague. Herein, we display that TROAP exhibits an augmented trend in STS, and its elevation correlates with a poor prognosis of STS. Furthermore, its reduction is related to increased immune cell infiltration, enhanced stroma, and elevation of immune activation. Meanwhile, the TROAP-derived genomic signature is validated to predict patient prognosis, immunotherapy, and drug response reliably. A nomogram constructed based on age, metastatic status, and a TROAP-derived risk score of an STS individual could be used to quantify the survival probability of STS. In addition, in vitro experiments have demonstrated that TROAP is overexpressed in STS, and the downregulation of TROAP could affect the proliferation, migration, metastasis, and cell cycle of STS cells. In summary, the TROAP expression is elevated in STS tissues and cells, which is related to the poor prognosis and malignant biological behaviors of STS. It could act as a potential prognostic biomarker for diagnosis and treatment of STS.
Racial diversity in academic dermatology: A cross-sectional analysis of Black academic dermatology faculty in the United States
Authors: Sarah Gonzalez, Nicole Syder, Shanice A. McKenzie, Kyla N. Price, Binh Ngo, Arielle Carolina Mora Hurtado, Jack Rodman, Nada Elbuluk
Journal: Journal of the American Academy of Dermatology (2023)
Long-Term Safety Outcomes of Fecal Microbiota Transplantation: Real-World Data Over 8 Years From the Hong Kong FMT Registry
Authors: Yuk Kam Yau, Louis Ho Shing Lau, Rashid Nok Shun Lui, Sunny Hei Wong, Cosmos Liutao Guo, Joyce Wing Yan Mak, Jessica Yuet Ling Ching, Margaret Ip, Michael A. Kamm, David T. Rubin, Paul Kay Sheung Chan, Francis Ka Leung Chan, Siew Chien Ng
Journal: Clinical Gastroenterology and Hepatology (2023)
Endoscopic vacuum therapy for anastomotic leakage after upper gastrointestinal surgery
Authors: Gunnar Loske
Journal: Endoscopy (2023)

Endoscopic vacuum therapy (EVT) is a highly effective treatment option for leaks throughout the gastrointestinal (GI) tract and is an extremely beneficial technique in visceral surgery. It represents one of the most important innovations in the management of endoscopic surgical complications in the last 20 years [1] [2]. For the management of complications in esophageal surgery, a distinction can be drawn between the pre- and post-EVT eras [3]. The technique is increasingly being used not only for therapeutic purposes but also for pre-emptive prophylaxis with the aim of protecting intraoperative anastomoses [4].
Antigenicity and infectivity characterisation of SARS-CoV-2 BA.2.86
Authors: Sijie Yang, Yuanling Yu, Fanchong Jian, Weiliang Song, Ayijiang Yisimayi, Xiaosu Chen, Yanli Xu, Peng Wang, Jing Wang, Lingling Yu, Xiao Niu, Jing Wang, Tianhe Xiao, Ran An, Yao Wang, Qingqing Gu, Fei Shao, Ronghua Jin, Zhongyang Shen, Youchun Wang, Yunlong Cao
Journal: The Lancet Infectious Diseases (2023)
Xpert MTB/RIF Ultra on contaminated liquid cultures for tuberculosis and rifampicin-resistance detection: a diagnostic accuracy evaluation
Authors: Yonas T Ghebrekristos, Natalie Beylis, Chad M Centner, Rouxjeane Venter, Brigitta Derendinger, Happy Tshivhula, Selisha Naidoo, Rencia Alberts, Bronwyn Prins, Anitta Tokota, Tania Dolby, Florian Marx, Shaheed V Omar, Robin Warren, Grant Theron
Journal: The Lancet Microbe (2023)
Labour exploitation among community health workers
Authors: Ashley Wennerstrom, Denise Octavia Smith
Journal: The Lancet Global Health (2023)

In The Lancet Global Health, Madeleine Ballard and colleagues1 report on dual-cadre systems, in which unsalaried community health workers work alongside paid health-care workers. The finding that nearly 60% of unsalaried workers and one in ten salaried workers experience labour exploitation is concerning. Considering that community health workers are primarily women of colour, exploitation of this workforce is a predictable consequence of patriarchy, racism, and ongoing legacies of colonisation that must be addressed.
Potential cost-effectiveness of community availability of tenofovir, lamivudine, and dolutegravir for HIV prevention and treatment in east, central, southern, and west Africa: a modelling analysis
Authors: Andrew N Phillips, Loveleen Bansi-Matharu, Maryam Shahmanesh, James R Hargreaves, Jennifer Smith, Paul Revill, Euphemia Sibanda, Peter Ehrenkranz, Kenly Sikwese, Alison Rodger, Jens D Lundgren, Charles F Gilks, Catherine Godfrey, Frances Cowan, Valentina Cambiano
Journal: The Lancet Global Health (2023)
Sex differences in mortality among children, adolescents, and young people aged 0–24 years: a systematic assessment of national, regional, and global trends from 1990 to 2021
Authors: Fengqing Chao, Bruno Masquelier, Danzhen You, Lucia Hug, Yang Liu, David Sharrow, Håvard Rue, Hernando Ombao, Leontine Alkema, Bochen Cao, Victor Gaigbe-Togbe, Thomas Spoorenberg, Kathleen Louise Strong, Emi Suzuki, Danzhen You
Journal: The Lancet Global Health (2023)

Differences in mortality exist between sexes because of biological, genetic, and social factors. Sex differentials are well documented in children younger than 5 years but have not been systematically examined for ages 5-24 years. We aimed to estimate the sex ratio of mortality from birth to age 24 years and reconstruct trends in sex-specific mortality between 1990 and 2021 for 200 countries, major regions, and the world.
Diabetes risk and provision of diabetes prevention activities in 44 low-income and middle-income countries: a cross-sectional analysis of nationally representative, individual-level survey data
Authors: Nicholas Errol Rahim, David Flood, Maja E Marcus, Michaela Theilmann, Taing N Aung, Kokou Agoudavi, Krishna Kumar Aryal, Silver Bahendeka, Brice Bicaba, Pascal Bovet, Alpha Oumar Diallo, Farshad Farzadfar, David Guwatudde, Corine Houehanou, Dismand Houinato, Nahla Hwalla, Jutta Jorgensen, Gibson Bernard Kagaruki, Mary Mayige, Roy Wong-McClure, Bagher Larijani, Sahar Saeedi Moghaddam, Omar Mwalim, Kibachio Joseph Mwangi, Sudipa Sarkar, Abla M Sibai, Lela Sturua, Chea Wesseh, Pascal Geldsetzer, Rifat Atun, Sebastian Vollmer, Till Bärnighausen, Justine Davies, Mohammed K Ali, Jacqueline A Seiglie, Jennifer Manne-Goehler
Journal: The Lancet Global Health (2023)
Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): an international, multicentre, randomised, placebo-controlled trial
Authors: Akimichi Morita, Bruce Strober, A David Burden, Siew Eng Choon, Milan J Anadkat, Slaheddine Marrakchi, Tsen-Fang Tsai, Kenneth B Gordon, Diamant Thaçi, Min Zheng, Na Hu, Thomas Haeufel, Christian Thoma, Mark G Lebwohl
Journal: The Lancet (2023)
A cardiovascular polypill for secondary stroke prevention in a tertiary centre in Ghana (SMAART): a phase 2 randomised clinical trial
Authors: Fred Stephen Sarfo, Jenifer Voeks, Sheila Adamu, Benedict Apaw Agyei, Manolo Agbenorku, Nyantakyi Adu-Darko, Mercy Adomah Oteng, Vida Obese, Rexford Adu Gyamfi, Nathaniel Adusei Mensah, Raelle Tagge, Michael Ampofo, Samuel Amoabeng Kontoh, Samuel Blay Nguah, Bruce Ovbiagele
Journal: The Lancet Global Health (2023)
Catastrophic health expenditure during the COVID-19 pandemic in five countries: a time-series analysis
Authors: Annie Haakenstad, Corinne Bintz, Megan Knight, Kelly Bienhoff, Horacio Chacon-Torrico, Walter H Curioso, Joseph L Dieleman, Anna Gage, Emmanuela Gakidou, Simon I Hay, Nathaniel J Henry, Akram Hernández-Vásquez, Judith S Méndez Méndez, Héctor J Villarreal, Rafael Lozano
Journal: The Lancet Global Health (2023)
Time is running out to meet the Sustainable Development Goals as health inequities widen and trust in government falls
Authors: Hans Henri P. Kluge, Benjamin Barr, Natasha Azzopardi Muscat, Christine Brown
Journal: BMJ (2023)

More than 200 years ago, William Wordsworth illustrated in his sonnet "The world is too much with us" how the advancement of the Industrial Revolution was leaving too many people behind.The world is once again at a vital turning point, facing numerous linked challenges.The cost-of-living and climate crises, widening inequities, and increasing pressures on health and welfare services, are leaving more and more of us behind.
Regulation of the hippocampal translatome by Apoer2-ICD release
Authors: Catherine R. Wasser, Gordon C. Werthmann, Eric M. Hall, Kristina Kuhbandner, Connie H. Wong, Murat S. Durakoglugil, Joachim Herz
Journal: Molecular Neurodegeneration (2023)

Abstract Background ApoE4, the most significant genetic risk factor for late-onset Alzheimer’s disease (AD), sequesters a pro-synaptogenic Reelin receptor, Apoer2, in the endosomal compartment and prevents its normal recycling. In the adult brain, Reelin potentiates excitatory synapses and thereby protects against amyloid-β toxicity. Recently, a gain-of-function mutation in Reelin that is protective against early-onset AD has been described. Alternative splicing of the Apoer2 intracellular domain (Apoer2-ICD) regulates Apoer2 signaling. Splicing of juxtamembraneous exon 16 alters the γ-secretase mediated release of the Apoer2-ICD as well as synapse number and LTP, and inclusion of exon 19 ameliorates behavioral deficits in an AD mouse model. The Apoer2-ICD has also been shown to alter transcription of synaptic genes. However, the role of Apoer2-ICD release upon transcriptional regulation and its role in AD pathogenesis is unknown. Methods To assess in vivo mRNA-primed ribosomes specifically in hippocampi transduced with Apoer2-ICD splice variants, we crossed wild-type, cKO, and Apoer2 cleavage-resistant mice to a Cre-inducible translating ribosome affinity purification (TRAP) model. This allowed us to perform RNA-Seq on ribosome-loaded mRNA harvested specifically from hippocampal cells transduced with Apoer2-ICDs. Results Across all conditions, we observed ~4,700 altered translating transcripts, several of which comprise key synaptic components such as extracellular matrix and focal adhesions with concomitant perturbation of critical signaling cascades, energy metabolism, translation, and apoptosis. We further demonstrated the ability of the Apoer2-ICD to rescue many of these altered transcripts, underscoring the importance of Apoer2 splicing in synaptic homeostasis. A variety of these altered genes have been implicated in AD, demonstrating how dysregulated Apoer2 splicing may contribute to neurodegeneration. Conclusions Our findings demonstrate how alternative splicing of the APOE and Reelin receptor Apoer2 and release of the Apoer2-ICD regulates numerous translating transcripts in mouse hippocampi in vivo . These transcripts comprise a wide range of functions, and alterations in these transcripts suggest a mechanistic basis for the synaptic deficits seen in Apoer2 mutant mice and AD patients. Our findings, together with the recently reported AD-protective effects of a Reelin gain-of-function mutation in the presence of an early-onset AD mutation in Presenilin-1, implicate the Reelin/Apoer2 pathway as a target for AD therapeutics. Graphical Abstract